We are studying Malaria drugs resistance, and we found that the % of early treatment failure in P. falciparum infected patients treated with ACT higher among children below 5 years.
Is this normal or explanable ?
Yes, please define 'early treatment failure' to make sue we understand what you mean by that. Not being a clinician, I could only guess about reasons, but adding to Dr. Kopfli's answer I could suggest that the children are getting reinfected soon after treatment ended. Or that the parasites are not clearing out of the liver during treatment and thus restart the blood phase of their life cycle after treatment ends.
Another thought. Is it possible the children with early failure actually had early stages of cerebral malaria and the drug was not able to cross the blood brain barrier (while it could in those children with greater levels of cerebral malaria and damage to the blood brain barrier)?
An echo to Dr. Kopfli
1. These under 5 yr children had relatively little acquired immunity compared with the older individuals.
2. Parasite density would be higher in these young children.
Therefore, parasite clearance time might take longer in these group of children.
This means parasite clearance time at Day 3 is likely to be lower.
By definition, ETF means inadequate decrease in parasitemia ( i.e parasitemia on day 3 ≥25% of count on day 0.)
I feel that you have found ≥25% parasitaemina at Day 3.
Thank you.
Thank you.
Actually, not only the ETF was more common in this age group for falciparum malaria treatment outcome in ACT efficacy trial. We conducted an in vivo study in Yemen for monitoring ASSP against falciparum malaria isolates. All recrudescent cases were found of LCF and they were all below 5 years of age. The reason for such point could be due to the low level of immunity in this specific age group, but as not all the mechanisms of malaria elimination from the human body are not fully understood yet, other factors could be attributed.
ACT may cause less parasite clearance time after treatment . However, this may cause less asymptomatic parasitaemia and less or absence of immunity in those child in malaria endemic areas may lead to drug failure
See this analysis concerning clinical determinants of the early parasitological response to ACTs in young African children with uncomplicated P. falciparum malaria: http://dx.doi.org/10.1186/s12916-015-0445-x
Two things that are far from being understood are: (A) The phenomenon of presumed temporary drug-induced quiescence during the blood cycle phase of the early P. falciparum infection (in vitro, ring stages can reactivate, which could be reflected in vivo as a recrudescence). (B) P. falciparum and other malaria parasites probably occur not only in the liver and bloodstream, but also elsewhere in the body, where drugs do not necessarily kill them. In the early infection, the skin is a possibility, irrespective of prevailing dogma (http://dx.doi.org/10.1038/nrmicro3111); but not the only one.
Comments regarding both "A" and "B" are "hidden" in various places in the text in the following article (despite its title): http://dx.doi.org/10.1016/j.pt.2015.02.003
Also, read what is stated at the end of the legend for Figure 2 in this publication: http://dx.doi.org/10.1016/j.pt.2016.02.006
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